TY - JOUR
T1 - Influence of BDNF and MTHFR polymorphisms on hippocampal volume in first-episode psychosis
AU - Pujol, Nuria
AU - Mané, Anna
AU - Bergé, Daniel
AU - Mezquida, Gisela
AU - Amoretti, Silvia
AU - Pérez, Lucía
AU - González-Pinto, Ana
AU - Barcones, Fe
AU - Cuesta, Manuel J.
AU - Sánchez-Tomico, Georgina
AU - Vieta, Eduard
AU - Castro-Fornieles, Josefina
AU - Bernardo, Miquel
AU - Parellada, Mara
N1 - Copyright © 2020 Elsevier B.V. All rights reserved.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Background: The BDNF and MTHFR genes are independently linked to the pathogenesis of schizophrenia and its neuroimaging correlates. The aim of this study was to explore, for the first time, the individual and interactional effects of the Val66Met and C677T polymorphisms on hippocampal atrophy in first-episode psychosis (FEP). Method: Multi-site case-control study based on clinical, genetic (rs 6265, rs 1801133) and structural magnetic resonance imaging data from 98 non-affective FEP patients and 117 matched healthy controls (HC). Hippocampal volume was estimated using FreeSurfer software and this volume was compared between diagnostic (FEP vs HC) and genotype (Val66Met, C677T) groups. The BDNF Val66Met x MTHFR C677T effect on hippocampal volume was further evaluated through stratified analyses. Results: After applying Bonferroni correction, diagnosis showed a significant effect for adjusted left and right hippocampal volume (FEP < HC). Stratified analyses showed that the interactive effect contributed to adjusted hippocampal size in both the HC (left and right hippocampus) and FEP groups (right hippocampus); among BDNF Met carriers, those with the CT-TT genotype exhibited decreased hippocampal volume compared to individuals with the homozygous normal CC genotype. Conclusions: Our results provide preliminary evidence indicating that the Val66Met x C677T interaction may be a potential genetic risk factor for reduced hippocampal size in both healthy controls and in patients with FEP. Further research in independent samples including different ethnic groups is warranted to confirm this new finding.
AB - Background: The BDNF and MTHFR genes are independently linked to the pathogenesis of schizophrenia and its neuroimaging correlates. The aim of this study was to explore, for the first time, the individual and interactional effects of the Val66Met and C677T polymorphisms on hippocampal atrophy in first-episode psychosis (FEP). Method: Multi-site case-control study based on clinical, genetic (rs 6265, rs 1801133) and structural magnetic resonance imaging data from 98 non-affective FEP patients and 117 matched healthy controls (HC). Hippocampal volume was estimated using FreeSurfer software and this volume was compared between diagnostic (FEP vs HC) and genotype (Val66Met, C677T) groups. The BDNF Val66Met x MTHFR C677T effect on hippocampal volume was further evaluated through stratified analyses. Results: After applying Bonferroni correction, diagnosis showed a significant effect for adjusted left and right hippocampal volume (FEP < HC). Stratified analyses showed that the interactive effect contributed to adjusted hippocampal size in both the HC (left and right hippocampus) and FEP groups (right hippocampus); among BDNF Met carriers, those with the CT-TT genotype exhibited decreased hippocampal volume compared to individuals with the homozygous normal CC genotype. Conclusions: Our results provide preliminary evidence indicating that the Val66Met x C677T interaction may be a potential genetic risk factor for reduced hippocampal size in both healthy controls and in patients with FEP. Further research in independent samples including different ethnic groups is warranted to confirm this new finding.
KW - BDNF Val66Met polymorphism
KW - First-episode psychosis
KW - Hippocampus
KW - MTHFR C677T polymorphism
UR - http://www.scopus.com/inward/record.url?scp=85091689508&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/14de2dbe-6ede-30e6-8215-d891ab5bd495/
U2 - 10.1016/j.schres.2020.08.002
DO - 10.1016/j.schres.2020.08.002
M3 - Artículo
C2 - 32988741
AN - SCOPUS:85091689508
SN - 0920-9964
VL - 223
SP - 345
EP - 352
JO - Schizophrenia Research
JF - Schizophrenia Research
ER -